Myo-inositol reduces ?-catenin activation in colitis

Emily M. Bradford, Corey A. Thompson, Tatiana Goretsky, Guang Yu Yang, Luz M. Rodriguez, Linheng Li, Terrence A. Barrett*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

AIM To assess Dietary myo-inositol in reducing stem cell activation in colitis, and validate p?-cateninS552 as a biomarker of recurrent dysplasia. METHODS We examined the effects of Dietary myo-inositol treatment on inflammation, p?-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran soDium sulfate-treated colitic mice. AdDitionally, we assessed nuclear p?-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS In mice, p?-cateninS552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, p?-cateninS552 staining Discriminated ulcerative colitis patients with a history of LGD from those with benign Disease. CONCLUSION Enumerating crypts with increased numbers of p?- cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.

Original languageEnglish (US)
Pages (from-to)5115-5126
Number of pages12
JournalWorld Journal of Gastroenterology
Volume23
Issue number28
DOIs
StatePublished - Jul 28 2017

Funding

Supported by Veterans Affairs Merit Award, No. IO1CX001353 (to Barrett TA); National Institutes of Health, No. 2R01DK095662-06A1 (to Barrett TA); the National Cancer Institute at the National Institutes of Health, No. N01-CN-35157 (to Bergan R); the Training Program in Oncogenesis and Developmental Biology through the National Cancer Institute, No. NCI T32 CA080621 (to Bradford EM); an Institutional Development Award from the National Institute of General MeDical Sciences of the National Institutes of Health, No. 8 P20GM103527-05; and American Physiological Society STEP-UP Fellowship (to Thompson CA).

Keywords

  • Biomarker
  • Chemoprevention
  • Colitis-associated cancer
  • Dysplasia
  • Stem cell

ASJC Scopus subject areas

  • Gastroenterology

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